This project will contribute to the overall objectives of this AADC by focusing on the contribution of sinusitis to the presence and severity of asthma. Sinusitis and asthma are very common conditions characterized by a similar inflammatory infiltrate, but the relationship between them is poorly understood. We have shown that extensive mucosal disease is a major independent risk factor for asthma. This finding could indicate that either the two conditions have a common cause or that one is dependent on the other. We will distinguish these possibilities by performing a prospective study on the relationship between sinusitis and asthma. Inherent in these studies is the critical need to develop and validate a methodology for objectively measuring the presence, severity, and clinical course of chronic hyperplastic sinusitis (CHS)/nasal polyposis (NP). As a disease of hyperplastic mucosal tissue with eosinophilia, we will show that the hyperplasia will be readily visualized and accurately quantified by CT scan. We will gain insights into the pathophysiology and interplay of these conditions by identifying changes in the nose and sinuses that correlate with increased inflammation in the lungs during experimental RV infection and nasal allergen challenges. Our proposed mechanism by which RV infection and allergen contribute to inflammation of the sinuses and lungs is that T cells primed in the nares and sinuses can act directly by localizing to the lungs. Alternatively, RV infection and allergen challenge may contribute to eosinophil influx into the airways, derived either from the bone marrow or locally from CD34+ve, IL5Ra+ precursors. Activated lymphocytes and eosinophil precursors, as well as newly generated bone marrow-derived eosinophils, express VLA-4 and, in the presence of pre-existing VCAM-I, will localize in the lung where they will exacerbate inflammation. Finally, we will demonstrate that CHS/NP is characterized by the dysregulation of cysLTs and their receptors. CysLTs promote eosinophil-mediated inflammation, mucous gland secretion, the proliferation of epithelium and endothelium, and they contribute to remodeling and fibrosis. We hypothesize that the modulation of cysLT production and activity by aspirin desensitization will attenuate CHS/NP.